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Biomedical subjects

D Combs

Publications and source records attributed to D Combs.

At least 19 recordsLinked to original sources
PubMed2003

Pharmacokinetic study of patients with follicular or mantle cell lymphoma treated with rituximab as 'in vivo purge' and consolidative immunotherapy following autologous stem cell transplantation.

BACKGROUND: Little is known about the pharmacokinetics of rituximab in an autologous stem cell transplant (ASCT) setting. PATIENTS AND METHODS: We evaluated serum rituximab levels in 26 patients with follicular or mantle cell lymphoma treated with a combination of ASCT and immunotherapy. Patients received nine infusions of rituximab (375 mg/m(2)): one dose as an 'in vivo purge' prior to stem cell collection, and two 4-week cycles at 8 and 24 weeks following ASCT. Pre- and post-infusion serum rituximab levels were measured during the purging dose, with doses 1 and 4 of both sets of maintenance rituximab cycles, and 12 weeks and 24 weeks following treatment. RESULTS: Rituximab levels were detectable after the first infusion, and peaked at a mean concentration of 463.8 micro g/ml after the final dose. Levels remained detectable 24 weeks after completion of treatment. There was a trend toward higher rituximab levels in patients with follicular lymphoma. Serum concentrations achieved during the maintenance cycles were similar to levels observed in patients with measurable lymphoma treated during 'the pivotal trial'. No correlation was observed between serum rituximab levels achieved in the minimal disease state and the risk of later clinical relapse, nor with the ability to achieve a molecular remission following ASCT. CONCLUSIONS: The finding that patients treated in minimal disease states and at the time of active disease both achieve similar final serum rituximab concentrations after four infusions suggests that the pharmacokinetics are complex, and may not necessarily correlate with disease burden. The precise factors influencing rituximab clearance in patients with lymphoma are unresolved, and this remains an area of active research.

Antibodies, Monoclonal↗
PubMed2001

First direct structural comparison of complexes of the same metal fragment to ketenes in both C,C- and C,O-bonding modes.

Using a series of Ir(I) and Rh(I) ketene complexes, conclusions about the structure and bonding of complexes of the fundamentally important ketene ligand class are reached. In a unique comparison of X-ray structures of the same metal fragment to ketenes in both the eta(2)-(C,C) and the eta(2)-(C,O) binding mode, the Ir-Cl bond distances in complexes of trans-Cl(Ir)[P(i-Pr)(3)](2) to phenylketene [4, eta(2)-(C,C)] and diphenylketene [2a, eta(2)-(C,O)] are 2.371(3) and 2.285(2) A, respectively. This would be consistent with greater trans influence of a ketene ligand bound to a metal through its C=C bond than one connected by its C=O bond. Back-bonding of Ir(I) and Rh(I) to diphenylketene was assessed using trans-Cl(M)[P(i-Pr)(3)](2)[eta(2)-(C,O)-diphenylketene] (2a and 2d). Most bond lengths and angles are identical, but slightly greater back-bonding by Ir(I) is suggested by the somewhat greater deformation of the ketene C=C=O system [C-C-O angles are 136.6(4) and 138.9(4) in the Ir and Rh cases 2a and 2d, respectively]. Syntheses of new labeled ketenes Ph(2)C=(13)C=O and Ph(2)C=C=(18)O and their Ir(I) and Rh(I) complexes are reported, along with the generation of an Ir(I) complex of PhCH=(13)C=O. The effects of isotopic substitution on infrared absorption data for ketene complexes are presented for the first time. Preliminary normal coordinate mode analysis allowed definitive assignment of absorptions ascribed to the C-O stretching frequencies of coordinated ketenes, which are near the absorptions for aromatic ring systems commonly found as substituents on ketenes. For free diphenylketene and four of its complexes and a phenylketene complex characterized by X-ray diffraction, the magnitude of the (13)C-(13)C coupling between the two ketene carbons is correlated to carbon-carbon bond distance.

Journal Article↗
PubMed2001

Hydrogen bonding in the crystal structure of bis[3-([thiomethyl]methyl)pyrazole]copper(II) perchlorate.

The ability of a metal-coordinated pyrazole to engage in hydrogen bonding has been explored by synthesis of the title complex, bis[3-([thiomethyl]methyl)pyrazole]copper(II) perchlorate (3). The coordination in 3 can be described as pseudo-octahedral, with two relatively tightly-bound 3-[(thiomethyl)methyl]pyrazole ligands occupying the equatorial plane, forming a [CuN(2)S(2)](2+) unit with the S donors mutually trans to each other. The axial positions are each filled by a weakly bound perchlorate counterion, one oxygen of which forms a hydrogen bond with the pyrazole N-H moiety on an adjacent [CuN(2)S(2)](2+) unit.

Journal Article↗
PubMed2001

Take-home lessons.

Explore the source record for details and available documents.

Electronic Data Processing↗
PubMed2000

Modification of affect perception deficits in schizophrenia.

This study investigated two strategies for improving facial affect perception in schizophrenia: monetary reinforcement and promoting facial feedback via mimicry of the expressions of target faces. A total of 40 inpatients with schizophrenia were administered the face emotion identification test during four phases: baseline, intervention, immediate post-test, and 1week follow-up. Subjects were randomly assigned to one of four interventions: repeated practice, monetary reinforcement, facial feedback, and a combination of reinforcement and facial feedback. Generalization of the intervention to a test of facial affect discrimination was also examined. The results showed that all groups of subjects, with the exception of those in the repeated practice group, improved in their ability to identify facial affect, with these effects showing some stability over time. There was limited evidence of these effects generalizing to the test of facial affect discrimination.

Adult↗
PubMed2000

Synthesis and structure of isomeric palladium(II)-pyrazole chelate complexes with and without an N-H group as hydrogen bond donor.

Four new ligands containing a pyrazole ring and either a phosphine or thioether were prepared and converted to their cis-dichloropalladium(II) complexes. Two of the ligands are especially notable for the attachment of a side chain at pyrazole carbon, rather than at nitrogen. The new metal complexes include dichloro[3-(diphenylphosphinomethyl)pyrazole]palladium(II) (1-PdCl2) and dichloro[3-(methylthiomethyl)pyrazole]palladium(II) (2-PdCl2), which both feature an N-H group as a potential proton or hydrogen bond donor. For comparison, isomeric complexes lacking an NH group were prepared: dichloro[1-(diphenylphosphinomethyl)pyrazole]palladium(II) (3-PdCl2) and dichloro[1-(methylthiomethyl)pyrazole]palladium(II) (4-PdCl2). As determined by X-ray crystallography, all four complexes were found to have slightly distorted square planar geometry. Complexes 1-PdCl2 and 2-PdCl2, which contain an NH group, exhibit both intermolecular and intramolecular hydrogen bonding, whereas isomers 3-PdCl2 and 4-PdCl2 do not. Single-crystal X-ray structure determinations on the following compounds are reported: 1-PdCl2, space group P1, a = 8.4488(9) A, b = 8.9175(13) A, c = 12.731(2) A, Z = 2, V = 871.8(2) A3; 2-PdCl2, space group Pbca, a = 10.8827(10) A, b = 11.7721(7) A, c = 14.874(2) A, Z = 8, V = 1905.6 A3; 3-PdCl2, space group P2(1)/c, a = 20.520(2) A, b = 12.549(2) A, c = 13.9784(13) A, Z = 8, V = 3401.1(6) A3; 4-PdCl2, space group Pbca, a = 10.6545(10) A, b = 12.0205(11) A, c = 14.6474(14) A, Z = 8, V = 1875.9(3) A3.

Journal Article↗
PubMed1998

Medical examiner and coroner systems: history and trends.

CONTEXT: Medical legal investigations in the United States (primarily unnatural or suspected unnatural deaths) are carried out by medical examiner or coroner systems. Medical examiners-usually physicians and generally with training in pathology, medicolegal death investigation, and performance of forensic autopsies-generally have greater expertise in unnatural death investigations than do coroners. OBJECTIVE: To document the locations and implementation year for states and counties that have medical examiner systems that have replaced coroner systems or that are defined in statute and assist coroners in their investigations. DESIGN: Review of published information and national survey in 1997. SETTING: United States. PARTICIPANTS: County medical examiners and state medical examiners or their administrators. MAIN OUTCOME MEASURES: The location of states and counties with medical examiner systems, the implementation year for each system, and the proportion of counties and population served by medical examiner systems. RESULTS: A total of 79 of 91 county medical examiners responded. A total of 36 states have at least 1 medical examiner system at the county, district, or state level in which there is no coroner involved in the death investigation process. Only 22 states have medical examiner death investigation systems in place and have no coroners in the state. Among 13 states in which some counties have coroner systems and some have medical examiner systems, medical examiner systems exist in 8% of counties and serve 43% of the population. Medical examiner systems that operate without coroner involvement serve about 48% of the population nationwide. Few state or county medical examiner systems have been implemented since 1990. CONCLUSIONS: In this century, medical examiner systems have gradually replaced coroner systems, but such change has slowed in recent years, with medical examiner systems now serving about 48% of the national population.

Coroners and Medical Examiners↗
PubMed1997

Neuromuscular retraining for facial paralysis.

Neuromuscular retraining is an effective method for rehabilitating facial musculature in patients with facial paralysis. This nonsurgical therapy has demonstrated improved functional outcomes and is an important adjunct to surgical treatment for restoring facial movement. Treatment begins with an intensive clinical evaluation and incorporates appropriate sensory feedback techniques into a patient-specific, comprehensive, home therapy program. This article discusses appropriate patients, timelines for referral, and basic treatment practices of facial neuromuscular retraining for restoring function and expression to the highest level possible.

Adult↗
PubMed1996

Chiral kinetics and dynamics of ketorolac.

It has been shown that the analgesic and cyclooxygenase inhibitor activity of ketorolac tromethamine (KT), which is marketed as the racemic mixture of (-)S and (+)R enantiomers, resides primarily with (-)S ketorolac and that the ulcerogenic activity of this agent also resides in (-)S ketorolac. Resolution of individual enantiomers for analysis in plasma samples has been accomplished by two methods: derivatization to form diastereomers that are separated by HPLC, or direct HPLC using a chiral phase column. When mice and rats were given oral solutions of (-)S and (+) KT, it was found that the kinetics and interconversion of the enantiomers were species and dose dependent. Interconversion was higher in mice than in rats; when (-)S KT was administered, 71% of the area under the concentration-time curve (AUC) was due to (+)R ketorolac in mice, compared with 12% in rats. More interconversion was observed at higher doses; the percent of AUC due to (-)S ketorolac when (+)R KT was administered increased from 12% to 25% in mice and from 2% to 8% in rats. In general, more interconversion occurred from (-)S to (+)R ketorolac in the animal studies. Human subjects were given single oral solution doses of racemic KT (30 mg), (-)S KT (15 mg), and (+)R KT (15 mg). The plasma concentrations of (-)S ketorolac were lower than (+)R ketorolac at all sample times after racemic KT (22% of the AUC was due to (-)S ketorolac). When (+)R KT was administered, (-)S ketorolac was not detectable and interconversion was essentially 0%. When (-)S KT was administered, significant levels of (+)R ketorolac were detectable and interconversion was 6.5%. After all doses, plasma half-life was shorter and clearance greater for (-)S ketorolac than for (+)R ketorolac. Thus, in humans very little or no interconversion of (+)R to (-)S was observed, and interconversion of (-)S to (+)R was minimal (6.5%). These data demonstrate that the kinetics and interconversion of the enantiomers of ketorolac is different in animals and humans as well as from most other NSAIDs. This may be due to more rapid excretion or metabolism of (-)S ketorolac and a different mechanism of interconversion.

Animals↗
PubMed1995

Absorption of transdermally delivered ketorolac acid in humans.

Transdermal delivery of ketorolac acid, a potent analgesic, through human skin in vitro and in vivo was evaluated. The following three transdermal solutions were selected to study the in vitro skin permeation rate of ketorolac acid: formulation A, isopropyl alcohol: water: isopropyl myristate (IPA/water/IPM; 11:7:1); formulation B, ethanol: propylene glycol:isopropyl myristate (ET/PG/IPM; 11:7:2); and formulation C, IPM/capmul (glyceryl mono- and dicaprylate; Monoctanoin). The permeation of ketorolac acid through cadaver skin from a saturated drug solution was evaluated at 32 degrees C with a modified Franz diffusion cell. The in vitro skin fluxes were 180, 177, and 14 micrograms/cm2/h for formulations A, B, and C, respectively. The systemic bioavailability of ketorolac acid from three transdermal formulations was evaluated in nine healthy subjects in a randomized three-way crossover fashion. Hill Top chambers were used as prototype dermal delivery devices to load the drug solution. This procedure was followed by the immediate application of devices to human subjects for 24 h. Blood samples were collected at various time intervals up to 48 h, and the samples were assayed by HPLC. The basic pharmacokinetic parameters were derived from the drug plasma concentration versus time plot. The maximum drug plasma concentrations were 1.265, 0.696, and 0.092 micrograms/mL for formulations A, B, and C, respectively. Formulation A provided the highest in vitro and in vivo transdermal delivery rate among the three formulations studied. An excellent correlation between the in vitro steady-state skin flux and the area under the curve of in vivo plasma drug concentration versus time was observed for all the three formulations.

Administration, Cutaneous↗
PubMed1994

Standard language in death investigation laws.

Death investigation statutes and practices vary among the 50 states. We reviewed the Model Postmortem Examinations Act, recommendations of the National Association of Medical Examiners, the College of American Pathologists' "criteria for autopsies," and the death investigation statutes and practices in each state. By consolidating the terminology from these various information sources, we developed a list of death categories for which investigation by medical examiners or coroners in the United States is either mandated, commonly performed, or recommended. The list contains specific categories of death, which fall under these three more general areas: 1) unexpected and unexplained deaths, 2) deaths from intentional and unintentional external causes, and 3) deaths that fall under specialized categories related to the decedent's age, environment, or medical conditions, or to the method of bodily disposition. To promote greater uniformity in the death investigation practices among states, we recommend that the Model Postmortem Examinations Act be modified to explicitly recommend certain types of deaths for investigation and that states modify their death investigation statues to conform to such provisions. Presently, in states where death investigation statutes lack specificity in detailing the types of deaths that should be reported for possible medico-legal investigation, our recommendations, if not in conflict with local statutes, might be used as practice guidelines for the reporting and investigation of certain types of deaths.

Autopsy↗
PubMed1987

Effect of total parenteral nutrition upon intracranial pressure in severe head injury.

Animal investigations suggest that administration of hyperosmolar total parenteral nutrition (TPN) solutions may potentiate cerebral edema following head injury. Intravenous nutrition (TPN) is often required after head injury due to intolerance to enteral feeding (EN). This study evaluates the effect of TPN on intracranial pressure (ICP) measurements in severely brain-injured patients. Ninety-six severely brain-injured patients were randomly assigned to receive TPN or EN and were studied from hospital admission until 18 days postinjury. The TPN was started within 48 hours postinjury and the EN was started when tolerated. Peak daily ICP was not significantly different on admission and over time (overall mean +/- standard error of the mean 32.01 +/- 1.62 for TPN versus 32.5 +/- 1.25 for EN). Intracranial pressure was greater than 20 mm Hg in 75% of TPN patients and 73% of EN patients. Conventional therapy failed to control elevated ICP in 36% of TPN patients and 38% of EN patients. Of these patients, subsequent barbiturate therapy failed to control ICP in 56% of TPN patients and 64% of EN patients. Serum osmolality was not significantly different between groups at admission or over the course of the study. The TPN group tended to have higher mean serum glucose levels for the first 13 days postinjury, while the EN group had a higher mean serum glucose content thereafter, but these differences were not statistically significant. This study shows that TPN can be given safely to the severely brain-injured patient without causing serum hyperosmolality or affecting ICP levels or ICP therapy.

Brain Injuries↗
PubMed1981

Fetal heart rates during maternal wakefulness and sleep.

This study was designed to provide normative data on fetal heart rate (FHR), FHR variability, accelerations, and decelerations during maternal sleep in the third trimester of pregnancy and to identify rhythmicity in FHR variability. Twenty-four polygraphic recordings were obtained in 16 pregnant women at 32 and 36 weeks' gestation. FHR parameters were not predictably influenced by maternal sleep states. Cyclic changes in FHR variability with median cycle length of 53 minutes were observed. Accelerations and decelerations occurred an average of 12.2 and 4 times per 100 minutes, respectively. Bradycardia and tachycardia persisting beyond 10 minutes were not seen. FHR variability ranged from marked to decreased within recordings of the same subject; this observation has implications for non-stress testing of the fetus.

Female↗
PubMed1980

Therapeutic activity of pretazettine on Rauscher leukemia: comparison with the related Amaryllidaceae alkaloids.

Comparative studies on the cytotoxicity and antileukemic activity of limited numbers of Amaryllidaceae alkaloids with pretazettine, a narcissus alkaloid, have been performed on the systems of Rauscher virus-carrier cells and the leukemic mice. Only precriwelline, a stereochemical epimer of pretazettine, has been found to be therapeutically active as that of pretazettine. The natural precursors such as haemanthamine, crinamine and 6-hydroxycrinamide were also moderately active, but the artificial final product, tazettine, was confirmed to be inert. The structure-activity relationship of pretazettine or precriwelline has been partially analyzed. Also, the predominancy of antiviral activity relative to cytotoxicity of the alkaloids has been demonstrated when compared with some standard antileukemic drugs.

Alkaloids↗